Tricyclic Antidepressants (TCAs)
Tricyclic antidepressants (TCAs) were the first antidepressants developed, in the 1950s. They are highly effective but have more side effects than SSRIs and SNRIs, which is why they are no longer first-line treatment. They work by inhibiting the reuptake of serotonin and norepinephrine, but they also block histamine, cholinergic, and alpha-adrenergic receptors — which accounts for their unwanted effects.
Commonly used TCAs: amitriptyline (sedating, useful for depression with insomnia and chronic pain), nortriptyline (better tolerated), clomipramine (especially effective for OCD and depression), and imipramine.
Characteristic side effects include sedation, dry mouth, constipation, urinary retention, weight gain, orthostatic hypotension, and — in overdose — serious cardiac toxicity. For that reason they are prescribed cautiously and dispensed with care in patients at risk of suicide (the lethal dose is lower than with SSRIs).
They are still used when SSRIs/SNRIs have failed, for chronic pain (low-dose amitriptyline), migraine prevention, and OCD (clomipramine).
Practical example
Paulo has treatment-resistant depression and neuropathic pain. After failing two SSRIs and an SNRI, his psychiatrist prescribed amitriptyline at a gradually increasing dose. Paulo felt quite drowsy at first (his doctor advised taking it at night), but within six weeks he noticed improvement in both his mood and his pain.
Put this knowledge into practice
Balanced Mind brings together tools for day-to-day support — an emotional journal, mood tracking and crisis mode.
Works right in your browser — nothing to install.
Start for free